RESUMEN
BACKGROUNDS: Progranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE. METHODS: Wild type (WT) and PGRN knockout (PGRN-/-) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed. RESULTS: Following exposure to pristane, PGRN-/- mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN-/- mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection. CONCLUSION: The results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.
Asunto(s)
Anticuerpos Antinucleares , Modelos Animales de Enfermedad , Inmunoglobulina G , Péptidos y Proteínas de Señalización Intercelular , Lupus Eritematoso Sistémico , Ratones Endogámicos C57BL , Ratones Noqueados , Progranulinas , Terpenos , Animales , Lupus Eritematoso Sistémico/inmunología , Ratones , Inmunoglobulina G/sangre , Anticuerpos Antinucleares/sangre , Riñón/metabolismo , Riñón/inmunología , Bazo/inmunología , Bazo/metabolismo , ColágenoRESUMEN
BACKGROUND: Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping. RESULTS: MRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology. CONCLUSION: In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLsE.
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Anticuerpos Antinucleares , Lupus Eritematoso Sistémico , Magnesio , Linfocitos T Reguladores , Animales , Lupus Eritematoso Sistémico/inmunología , Femenino , Ratones , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/sangre , Magnesio/administración & dosificación , Linfocitos T Reguladores/inmunología , Modelos Animales de Enfermedad , Administración Oral , Ratones Endogámicos MRL lpr , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Piel/patología , Piel/inmunología , Piel/efectos de los fármacos , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/patologíaAsunto(s)
Antígeno de Maduración de Linfocitos B , Inmunosupresores , Lupus Eritematoso Sistémico , Inducción de Remisión , Adulto , Femenino , Humanos , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antígeno de Maduración de Linfocitos B/antagonistas & inhibidores , Antígeno de Maduración de Linfocitos B/inmunología , Resistencia a Medicamentos , Inmunosupresores/administración & dosificación , Inyecciones Subcutáneas , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Inducción de Remisión/métodosRESUMEN
The THαß host immunological pathway contributes to the response to infectious particles (viruses and prions). Furthermore, there is increasing evidence for associations between autoimmune diseases, and particularly type 2 hypersensitivity disorders, and the THαß immune response. For example, patients with systemic lupus erythematosus often produce anti-double stranded DNA antibodies and anti-nuclear antibodies and show elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 throughout the disease course. These cytokines and antibody isotypes are associated with the THαß host immunological pathway. Similarly, the type 2 hypersensitivity disorders myasthenia gravis, Graves' disease, graft-versus-host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjögren's syndrome have also been linked to the THαß pathway. Considering the potential associations between these diseases and dysregulated THαß immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferon α/ß could be explored for effective management.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/complicaciones , Síndrome de Sjögren/inmunología , Enfermedad Injerto contra Huésped/inmunología , Enfermedades Autoinmunes/inmunología , Citocinas/inmunología , Miastenia Gravis/inmunología , Anemia Hemolítica Autoinmune/inmunología , Enfermedad de Graves/inmunología , Enfermedad de Graves/complicaciones , Dermatomiositis/inmunologíaRESUMEN
This review article discusses neonatal lupus syndrome (NLS), an immune-mediated disease caused by maternal antibodies. Maternal antibodies in the fetal circulation are mostly but not always protective. NLS is a disease caused by pathogenic maternal autoantibodies in the fetal circulation. The passive immunization of the fetus by NLS-causing maternal antibodies may occur in the absence of a previously known maternal systemic autoimmune rheumatic disease (SARD). Screening for NLS-related antibodies in patients with related SARD or those in whom there is a risk of NLS including first-degree relatives should occur before pregnancy. This screening is best performed as part of a collaborative relationship between obstetrics and rheumatology. Pregnancy preparations in those with SARD include transitioning to pregnancy-safe medications. The symptoms of NLS range from minor skin rashes to fetal demise from heart block. Fetal screening allows for maternal therapeutic interventions that may be beneficial, as well as the use of fetal pacemakers in the more severe cases that include cardiac NLS.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/congénito , Lupus Eritematoso Sistémico/diagnóstico , Embarazo , Recién Nacido , Femenino , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Complicaciones del Embarazo/inmunologíaRESUMEN
Autoimmune diseases such as systemic lupus erythematosus (SLE) display a strong female bias. Although sex hormones have been associated with protecting males from autoimmunity, the molecular mechanisms are incompletely understood. Here we report that androgen receptor (AR) expressed in T cells regulates genes involved in T cell activation directly, or indirectly via controlling other transcription factors. T cell-specific deletion of AR in mice leads to T cell activation and enhanced autoimmunity in male mice. Mechanistically, Ptpn22, a phosphatase and negative regulator of T cell receptor signaling, is downregulated in AR-deficient T cells. Moreover, a conserved androgen-response element is found in the regulatory region of Ptpn22 gene, and the mutation of this transcription element in non-obese diabetic mice increases the incidence of spontaneous and inducible diabetes in male mice. Lastly, Ptpn22 deficiency increases the disease severity of male mice in a mouse model of SLE. Our results thus implicate AR-regulated genes such as PTPN22 as potential therapeutic targets for autoimmune diseases.
Asunto(s)
Andrógenos , Autoinmunidad , Lupus Eritematoso Sistémico , Proteína Tirosina Fosfatasa no Receptora Tipo 22 , Receptores Androgénicos , Linfocitos T , Animales , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 22/metabolismo , Masculino , Femenino , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Ratones , Linfocitos T/inmunología , Linfocitos T/metabolismo , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , Andrógenos/metabolismo , Ratones Noqueados , Activación de Linfocitos , Ratones Endogámicos NOD , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Transducción de SeñalRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is the quintessential autoimmune disease, as it is characterized by hyperactivity of CD4+ T cells and subsequently drives lupus pathology. Follicular helper T (TFH) cells play an important role in B cell maturation and antibody production. However, which specific subset of cTFH cells drives B cell function and contributes to the development of anti-dsDNA antibodies and SLE pathogenesis remains unclear. METHODS: Peripheral blood mononuclear cells from SLE patients with inactive (n = 11) and active (n = 21) were used to determine and detect frequencies and phenotypes of circulating TFH cells (cTFH), memory cTFH, and B cell subsets. The correlations among cTFH cell subsets and phenotypes, B cell subsets, anti-dsDNA autoantibodies, and clinical parameters were analyzed. RESULTS: In subjects with active SLE, cTFH1 and cTFH17 cells were significantly expanded and activated. These expanded cTFH cells expressed memory phenotypes; cTFH1 cells were predominantly central memory (CM) type, while cTFH17 cells were largely effector memory (EM) type. Phenotyping B cell subsets in these patients showed increased frequencies of aNAV and DN2 B cells. Clinically, ICOS+ cTFH1, ICOS+ cTFH17 cells, and SLEDAI-2k scores were found to be correlated. Analysis of cTFH-B cell relationship revealed positive correlations among ICOS+ cTFH1 cells, aNAV B cells, and anti-dsDNA antibodies. Activation of ICOS+ cTFH17 cells was significantly related to the expansion of aNAV and DN2 B cells. The presence of CM cells in cTFH1 and cTFH17 subsets was correlated with aNAV and DN2 B cell frequencies. CONCLUSION: SLE cTFH cells were found to be polarized toward cTFH1 and cTFH17 cells; activation of these cTFH subsets was significantly associated with disease activity score, aNAV, DN2 B cell expansion, and anti-dsDNA antibody level. Thus, the interactions among cTFH1, cTFH17, and B cells likely contribute to the development of autoantibodies and the pathogenesis in SLE.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Femenino , Adulto , Masculino , Persona de Mediana Edad , Linfocitos B/inmunología , Activación de Linfocitos/inmunología , Células T Auxiliares Foliculares/inmunología , Células Th17/inmunología , Adulto Joven , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/sangreRESUMEN
BACKGROUND: There have been only few reports on Rhupus syndrome with severe visceral involvement. Moreover, there was little consensus regarding its treatment. Belimumab is one of the options for treating this disease. For patients with clinical symptoms and elevated levels of anti CCP antibodies and anti-double stranded DNA antibodies, and it suggests Rhupus syndrome. After effective treatment, the decrease in levels of anti CCP antibodies and anti-double stranded DNA (ds-DNA) antibodies can effectively delay the progression of the disease and protect target organs. METHODS: We used a chemiluminescence instrument, (Yahuilong; Shenzhen, China), to measure the changes in CCP and dsDNA before and after treatment. RESULTS: Prior to treatment, the patient presented with symptoms of rheumatoid arthritis and systemic lupus erythematosus. Her laboratory tests showed dsDNA (214 IU/mL) and CCP level of Ë 3,000 U/mL. After treatment with belimumab, the clinical symptoms were significantly relieved, and the patient's CCP IgG level decreased to 263.5 U/mL. A blood test found that her anti-dsDNA was negative. CONCLUSIONS: CCP and dsDNA can serve as indicators for the diagnosis and treatment of Rhupus syndrome.
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Anticuerpos Antinucleares , Anticuerpos Monoclonales Humanizados , ADN , Humanos , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , ADN/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Persona de Mediana Edad , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Artritis Reumatoide/sangre , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Adulto , Biomarcadores/sangreRESUMEN
AIM: To investigate the correlation between T-cell senescence with the atherosclerosis markers in patients with systemic lupus erythematosus (SLE). METHODS: The study participants were 40 female SLE patients aged 18-45 years who met the 2019 EULAR/ACR criteria and 40 healthy individuals. The atherosclerosis markers were investigated using the Doppler ultrasonography examinations to measure the cIMT (carotid intima-media thickness) and flow-mediated dilation (FMD) and serological markers using soluble ICAM-1 and VCAM-1. Flow cytometry of CD4+CD57+, CD8+CD57+, CD4+CD28null, and CD8+CD28null T cells were used to assess the immunosenescence markers. RESULTS: The cIMT (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were significantly higher in SLE patients compared with control, while FMD was significantly lower in SLE patients (p < .001). The percentages of all T-cell senescence markers are also significantly higher in SLE patients than in healthy individuals. Positive correlations were shown between cIMT with the CD4+CD57+ (R = .301, p = .005), CD4+CD28null (R = .448, p < .001), and CD8+CD28null (R = .422, p < .001). Conversely, negative correlations were demonstrated between the FMD with CD4+CD57+ (R = -.236, p = .023), CD8+CD57+ (R = -.409, p < .001), CD4+CD28null (R = -.422, p < .001), and CD8+CD28null (R = -.318, p = .003). The soluble markers of sICAM-1 and sVCAM-1 were also positively correlated with the T-cell senescence markers. CONCLUSION: Early sign of atherosclerosis was demonstrated in patients with SLE in this study. T-cell senescence markers had significant correlations with the atherosclerosis markers, including the cIMT, FMD, and soluble adhesion molecules levels. Understanding the link between immunosenescence and atherosclerosis might help to identify a new method for early detection and treatment of atherosclerosis in SLE.
Asunto(s)
Aterosclerosis , Biomarcadores , Grosor Intima-Media Carotídeo , Senescencia Celular , Inmunosenescencia , Lupus Eritematoso Sistémico , Humanos , Femenino , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Adulto , Adulto Joven , Persona de Mediana Edad , Aterosclerosis/sangre , Aterosclerosis/inmunología , Aterosclerosis/etiología , Aterosclerosis/diagnóstico , Aterosclerosis/diagnóstico por imagen , Biomarcadores/sangre , Estudios de Casos y Controles , Adolescente , Molécula 1 de Adhesión Intercelular/sangre , Linfocitos T/inmunología , Molécula 1 de Adhesión Celular Vascular/sangre , Senescencia de Células TRESUMEN
Systemic lupus erythematosus is an autoimmune disease characterized by excessive inflammation and production of pathogenic Abs. Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase. It has been reported that selective HDAC6 inhibition decreases inflammation in lupus mouse models. In this study, sex- and age-matched wild-type (WT) and HDAC6-/- mice on the C57BL/6 background were administered 0.5 ml of pristane or PBS i.p. at 8-12 wk of age and were euthanized 10 d later. At sacrifice, body weight and spleen weight were measured, sera were collected, and splenocytes and peritoneal cells were harvested for flow cytometry. We found pristane administration increased the spleen weight with no difference between WT and HDAC6-/- mice. Pristane administration promoted the population of CD11b+Ly6C++ inflammatory monocytes and CD11b+Ly6G+ neutrophils. Peritoneal recruitment of these inflammatory monocytes and neutrophils was significantly decreased in HDAC6-/- mice compared with the WT mice. Flow cytometry results showed that the number of CD69+ T and B cells was increased in HDAC6-/- mice. Pristane administration also induced the IFN signature genes as determined by RT-qPCR. Furthermore, IFN signature genes were not affected in HDAC6-/- mice compared with the WT mice. In vitro studies in J774A.1 cells revealed that the selective HDAC6 inhibitor (ACY-738) increased acetylation of NF-κB while increasing Stat1 phosphorylation, which resulted in inducible NO synthase production in LPS/IFN-γ-stimulated cells. Taken together, these results demonstrate that although HDAC6 inhibition may inhibit some inflammatory pathways, others remain unaffected.
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Histona Desacetilasa 6 , Inflamación , Ratones Endogámicos C57BL , Ratones Noqueados , Terpenos , Animales , Histona Desacetilasa 6/antagonistas & inhibidores , Histona Desacetilasa 6/genética , Histona Desacetilasa 6/metabolismo , Terpenos/farmacología , Ratones , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Bazo/inmunología , Bazo/metabolismo , Bazo/citología , Monocitos/metabolismo , Monocitos/inmunología , Monocitos/efectos de los fármacos , Femenino , Modelos Animales de Enfermedad , Neutrófilos/inmunología , Neutrófilos/metabolismo , Factor de Transcripción STAT1/metabolismo , Masculino , Linfocitos B/inmunología , Linfocitos B/metabolismoRESUMEN
We present a case of a woman in her 20s with inadequately treated systemic lupus erythematosus (SLE). She presented with heavy menstrual bleeding, along with nasal and gum bleeding worsening over 3 months. There was no bleeding history in her family, childhood, dental procedures or childbirth. Evaluation ruled out structural causes, revealing prolonged activated partial thromboplastin time (incomplete correction on mixing studies), normal prothrombin time, moderate thrombocytopenia, and lupus anticoagulant and anti-phosphatidylserine/prothrombin antibody positivity twice, 12 weeks apart. Further evaluation showed very low von Willebrand factor (vWF) levels (<5%). She was treated with pulse methylprednisolone for 3 days, resulting in complete symptom resolution and improvement in vWF levels to 130%. The absence of bleeding history, family history, presence of very low vWF and its response to corticosteroids led to a diagnosis of acquired vWF syndrome as the cause of mucosal bleeding in an SLE patient with concomitant positive antiphospholipid antibody. She was discharged on hydroxychloroquine, mycophenolate mofetil and tapering oral corticosteroids.
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Anticuerpos Antifosfolípidos , Lupus Eritematoso Sistémico , Enfermedades de von Willebrand , Humanos , Femenino , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Anticuerpos Antifosfolípidos/sangre , Enfermedades de von Willebrand/complicaciones , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/tratamiento farmacológico , Enfermedades de von Willebrand/etiología , Adulto , Menorragia/etiología , Menorragia/tratamiento farmacológico , Metilprednisolona/uso terapéuticoRESUMEN
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by a variety of both signs and symptoms; it mainly affects women of childbearing age, with an estimated prevalence of 24/100,000 people in Europe and North America. SLE is often described as an antibodies-driven disease as its clinical manifestations are usually associated with the presence or the absence of specific antibodies. Objectives: To evaluate clinical manifestations in patients with SLE and to assess the relationship with the presence of specific antibodies by using real-world data. Methods: A retrospective study was performed; the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus were used to classify patients with SLE. Data concerning serological profiles (which included Antinuclear antibodies - ANA, anti dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-Smith) were gathered along with medical records of clinical manifestations. Complement levels were also tested for possible clinical correlations. χ² or Fisher's exact tests were utilized to establish associations between autoantibodies and symptoms. The odds ratios (OR) and their 95% confidence intervals (CI) were computed. No correction was made for multiple testing; only a p-value 0.01 ≤ was considered significant. Results: One-hundred and twenty-seven patients (n=127, mean age 53.43 ± 14.02) were enrolled in this study. Anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies showed an association with photosensitivity and pericarditis; furthermore, a strong association was found between anti-Ro antibodies and proteinuria, but only if anti-dsDNA antibodies were present as well. Patients who tested positive for anti-La/SSB antibodies correlated with a threefold increase in the risk of developing pericarditis. Lastly, anti-Smith appeared to be associated with NPSLE as well as an increased risk for both autoimmune hemolytic anemia and thrombocytopenia. Conclusions: In our study, many associations confirmed those found in previous studies; however, new relationships between antibodies and clinical manifestations were found thus indicating the need for additional evaluations to assess these correlations further.
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Anticuerpos Antinucleares , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Femenino , Masculino , Adulto , Estudios Retrospectivos , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Persona de Mediana Edad , Anciano , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Adulto JovenAsunto(s)
Bloqueo Cardíaco , Lupus Eritematoso Sistémico , Complicaciones del Embarazo , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/terapia , Resultado del Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/terapia , Bloqueo Cardíaco/congénito , Bloqueo Cardíaco/diagnóstico , Bloqueo Cardíaco/inmunología , Bloqueo Cardíaco/prevención & control , Recién NacidoAsunto(s)
Bloqueo Cardíaco , Lupus Eritematoso Sistémico , Complicaciones del Embarazo , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Complicaciones del Embarazo/inmunología , Femenino , Embarazo , Recién Nacido , Bloqueo Cardíaco/congénito , Bloqueo Cardíaco/diagnóstico , Bloqueo Cardíaco/epidemiología , Bloqueo Cardíaco/inmunologíaRESUMEN
Systemic lupus erythematosus (SLE) is a multifactorial disease characterized by the convergence of genetic, immunological, and viral elements resulting in a complex interaction of both internal and external factors. The role of the Epstein-Barr virus (EBV) and human endogenous retroviruses (HERV-E) as triggers and maintenance elements in the pathogenesis of SLE has been widely recognized. Previous studies have independently evaluated the effects of EBV and HERV-E in this disease. In this work, for the first time, these viral factors are jointly investigated in SLE patients. This study aimed at assessing the differential expression of immune regulatory genes and the incidence of specific viral pathogens (EBV and HERV-E), alongside the detailed characterization of surface markers in T- and B-lymphocytes in patients with SLE and control participants. A comparative analysis between patients with SLE and control participants was performed, evaluating the expression of phenotypic markers and genes involved in the immune response (TNF-α, IL-2, IL-6, IL-10, IFNG, TLR3), as well as HERV-E gag and EBV viral genes (LMP1 and BZLF1).A significant association between SLE and EBV was found in this study. A notable increase in EBV LMP1 gene expression was observed in patients with SLE . Also, a significant overexpression of HERV-E was observed, in addition to a considerable increase in the distribution of the cell surface marker CD27 + on T- and B-lymphocytes, observed in individuals with SLE compared to the control group. This study provides evidence regarding the role that EBV virus plays in lymphocytes in the context of SLE, highlighting how both the virus and the host gene expression may influence disease pathogenesis by altering immune regulatory pathways mediated by TNF-α, IFN-γ, and IL-10, as well as parallel overexpression of HERV-E gag. The decrease in TLR3 could indicate a compromised antiviral response, which could facilitate viral reactivation and contribute to disease activity.
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Retrovirus Endógenos , Herpesvirus Humano 4 , Leucocitos Mononucleares , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/virología , Retrovirus Endógenos/genética , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/genética , Adulto , Femenino , Masculino , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Leucocitos Mononucleares/metabolismo , Perfilación de la Expresión Génica , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/genética , Persona de Mediana Edad , Linfocitos B/inmunología , Linfocitos B/virología , Estudios de Casos y Controles , Linfocitos T/inmunología , Citocinas/metabolismo , Citocinas/genéticaRESUMEN
The ability of the immune system to fight against pathogens relies on the intricate collaboration between antibodies and Fc gamma receptors (FcγRs). These receptors are a group of transmembrane glycoprotein molecules, which can specifically detect and bind to the Fc portion of immunoglobulin G (IgG) molecules. They are distributed on a diverse array of immune cells, forming a strong defence system to eliminate invading threats. FcγRs have gained increasing attention as potential biomarkers for various diseases in recent years due to their ability to reflect immune dysregulation and disease pathogenesis. Increasing lines of evidence have shed new light on the remarkable association of FcγRs polymorphisms with the susceptibility of autoimmune diseases such as systemic lupus erythematosus (SLE) and lupus nephritis. Several studies have also reported the application of FcγR as a novel biomarker for the diagnosis of infection and cancer. Due to the surge in interest and concern regarding the potential of FcγRs as promising diagnostic biomarkers, this review, thereby, serves to provide a comprehensive overview of the structural characteristics, functional roles, and expression patterns of FcγRs, with a particular focus on their evolving role as diagnostic and prognostic biomarkers.
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Biomarcadores , Receptores de IgG , Receptores de IgG/metabolismo , Receptores de IgG/genética , Humanos , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Animales , Inmunoglobulina G/inmunología , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunologíaRESUMEN
OBJECTIVE: To improve our understanding of systemic lupus erythematosus (SLE)-macrophage activation syndrome (MAS). METHODS: A systematic review was performed, to retrieve all those papers on patients with SLE-MAS, in individual or aggregated form. The data in each of these medical records were extracted and analyzed to identify the characteristics of SLE-MAS. RESULTS: A total of 86 SLE-MAS patients were included (25 males and 61 females. The mean (±standard error of the mean) age was 31.21 ± 1.694 years. MAS occurred as the initial presentation of SLE in 47 people (54.65%) and during the course of SLE in 39 (45.35%). A coinfection was reported in 23 (26.74%) patients. The mean Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 16.54 ± 0.9462. Overall, 10 patients (11.63%) died. The SLEDAI-2K score was higher in patients with MAS as an initial manifestation of SLE than in those where MAS occurred during the course of SLE. The proportion of patients receiving steroid pulse therapy was lower in patients with coinfections. The deceased group demonstrated lower platelet and ferritin levels. Multiple regression analysis revealed that age and thrombocytopenia were independent factors associated with poor prognosis. In receiver operating characteristic analysis, a platelet count cutoff value of ≤47 × 109/L was a predictor of poor outcome. CONCLUSIONS: SLE-MAS patients demonstrated high lupus activity, and lupus activity was especially higher in patients with MAS as an initial manifestation. Lupus activity was the predominant trigger of lupus MAS. Thrombocytopenia was an independent factor for poor prognosis.
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Lupus Eritematoso Sistémico , Síndrome de Activación Macrofágica , Humanos , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/etiología , Síndrome de Activación Macrofágica/sangre , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Femenino , Masculino , Adulto , Trombocitopenia/etiología , Trombocitopenia/sangre , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can affect multiple organ systems and is heterogenous in its presentation and response to therapy. When diagnosed in childhood, SLE is associated with increased morbidity and mortality compared to adult SLE, often requiring substantial immunosuppression with the risk of significant side effects. There remains a significant unmet need for new therapies that can improve disease control and reduce glucocorticoid and other toxic medication exposure for patients with severe or refractory disease. The pathogenesis of SLE involves B cell dysregulation and autoantibody production, which are a hallmark of the disease. Currently approved B cell directed therapies often result in incomplete B cell depletion and may not target long-lived plasma cells responsible for SLE autoantibodies. It is hypothesized that by persistently eliminating both B cells and plasmablasts, CAR T therapy can halt autoimmunity and prevent organ damage in patient's refractory to current B cell-depleting treatments. Herein we summarize the current preclinical and clinical data utilizing CAR T cells for SLE and discuss the future of this treatment modality for lupus.
Asunto(s)
Inmunoterapia Adoptiva , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/terapia , Niño , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Linfocitos B/inmunología , Linfocitos T/inmunología , Receptores Quiméricos de Antígenos/inmunologíaRESUMEN
Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases and can manifest with a plethora of clinical signs and symptoms associated with a myriad of laboratory abnormalities. An infrequent but potentially lethal complication of SLE is macrophage activation syndrome (MAS). The diagnosis of MAS in SLE can be very challenging due to similarities in presentation of both flares and infections, such as fever, lymphadenopathy, splenomegaly, and cytopenias. These aggravating factors contribute to the increased risk of poor outcomes in SLE-associated MAS. Indeed, at the moment MAS remains invariably lethal if untreated and still has a high mortality rate with treatment. In this chapter, we discuss several aspects of MAS in the context of SLE and in particular, the pathogenesis of MAS in SLE, how MAS presents in pediatric versus adult SLE, and, finally, MAS treatment in SLE and future directions.
Asunto(s)
Lupus Eritematoso Sistémico , Síndrome de Activación Macrofágica , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/complicaciones , Humanos , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/etiología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/etiología , Citocinas/metabolismoRESUMEN
OBJECTIVE: We focused to analyze the time-course changes at pre- and post-flare of T peripheral helper (Tph) cells and circulating T follicular helper (Tfh) cells in the blood of patients with systemic lupus erythematosus (SLE) with lupus low disease activity state (LLDAS) before flare. METHODS: This study included inactive (n = 29) and active (n = 55) patients with SLE. Tph subsets, Tfh subsets, CD11chi B cells, and plasma cells in the blood were determined by flow cytometry. The blood levels of cytokines including interferons (IFNs) were measured by electrochemiluminescence assay or cytokine beads array. RESULTS: Active SLE patients exhibited the increased frequency of Tph1, Tph2, Tfh1, and Tfh2 subsets when compared to inactive patients, but no clear changes in the other subsets. During the treatment with medications, Tph1, Tph2, and Tfh2 subsets were significantly reduced along with disease activity and Tph1 and Tph2 subsets were positively correlated with SLE disease activity index (SLEDAI). The time course analysis of patients at pre- and post-flare revealed that in the patients at LLDAS before flare, Tph subsets and Tfh subsets were relatively low levels. At the flare, Tph cells, particularly Tph1 and Tph2 subsets, were increased and correlated with SLEDAI. Furthermore, the blood levels of IFN-α2a, IFN-γ, and IFN-λ1 were low in the patients with LLDAS before flare but these IFNs, particularly IFN-λ1, were increased along with flare. CONCLUSION: Increased frequency of Tph1 and Tph2 subsets and elevated levels of serum IFN-λ1 are presumably critical for triggering of flare in SLE.